Meriweather's mother gave birth to him when she was 13 years old. Meriweather started living with his adopted parents at age 11.[1] Meriweather attended Apopka High School in Apopka, Florida where he helped lead his school to the Florida Class 6A state championship as a senior in 2001. He started as a kick returner, returning four kicks for touchdowns as a senior. He also lettered in track and basketball.

Meriweather received an athletic scholarship to attend the University of Miami and play for the Miami Hurricanes football team. In 2002, Meriweather played in three games and had three total tackles before injuring his ankle, and was given a medical redshirt by the NCAA. In 2003, Meriweather played the majority of the season on special teams and in different nickel and dime packages. He got his first start against West Virginia as a nickel back. He finished the year with 22 tackles, one interception and five pass break-ups.

Meriweather played in all 12 games of the 2004 season but only started seven because of a nagging shoulder injury. He contributed 62 tackles, a half sack, two forced fumbles, five pass break-ups and two interceptions. He received the team's 2004 Hard Hitter Award.

Meriweather was named to the All-America team as voted by the Football Writers Association of America (FWAA) and was also selected first-team All-ACC in 2005. He was also a semi-finalist for the Jim Thorpe Award. He led the team with a career-high 115 tackles, seven pass break-ups, one sack, one fumble recovery, two forced fumbles and three interceptions. He received the team's Hard Hitter Award for the second consecutive season.

In 2006 Meriweather was a member of the 50th Anniversary Playboy Preseason All-America Team and was also on the Thorpe Award watch list for the second straight year. In 12 games, Meriweather registered 91 tackles, one sack, eight pass break-ups and one interception. He was also a semi-finalist for the Jim Thorpe Award, and was voted first-team All-ACC and All-American. He left Miami with the record for most tackles by a defensive back with 293.[2]

On July 21, 2006 Meriweather was involved in a shooting incident when teammate Willie Cooper was shot in the buttocks. In self-defense, Meriweather returned fire and shot at the unidentified shooters three times. Meriweather was not charged with a crime because his gun was owned legally.[3]

During the Miami-FIU brawl on October 14, 2006, Meriweather was seen stomping multiple times on several Florida International players on the ground. Meriweather was ultimately suspended by the ACC and Miami for his role in the incident.[4] It is believed that his actions during the brawl and the shooting incident may have caused his draft stock to slip.[5]

Meriweather was selected in the first round (24th overall) of the 2007 NFL Draft by the New England Patriots. During his rookie season most of his time was spent on special teams, and he finished the season with 28 tackles. He played in Super Bowl XLII as a third safety in the Patriots' defense behind Rodney Harrison and James Sanders. During his second season in 2008, Meriweather recorded his first career interception in Week 2 off New York Jets quarterback Brett Favre. After starting strong safety Rodney Harrison suffered a season-ending injury against the Denver Broncos in Week 7, Meriweather started the final 11 games. In Week 14, Meriweather recorded his first career sack to stifle a late-game Seattle Seahawks drive and secure a Patriots victory. He finished the season with 83 tackles, two sacks, and four interceptions.

In Week 7, Meriweather had two interceptions against the Tampa Bay Buccaneers, including one returned 39 yards for a touchdown, and was named AFC Defensive Player of the Week.[6] He started all 16 games and finished the 2009 season with 83 tackles and five interceptions, and was named to his first Pro Bowl as a replacement to the injured Jairus Byrd.

Brandon Meriweather was not part of the Patriots base defense to begin the 2010 season, something which Meriweather described as a coaching decision as a result of him freelancing in the defense during training camp.[7] After being replaced as a starter in Weeks 2 and 3 by James Sanders, Meriweather returned to his starting role in Week 4.

In Week 6, Meriweather was penalized for a helmet-to-helmet hit on Baltimore Ravens tight end Todd Heap. While Heap walked off the field and would later return, the hit, grouped together with other helmet-to-helmet hits on defenseless receivers from NFL players during the week, sparked controversy over the protection of players. The NFL took action the following Tuesday when they fined Meriweather $50,000 for the hit. Following the game, the league announced that it would begin suspending players for dangerous hits, particularly those involving helmet to helmet hits on defenseless receivers.[8]

In 16 games played (13 starts), Meriweather recorded 68 tackles, three interceptions, and six passes defensed. He was named to his second Pro Bowl following the season.

He would finally make his debut for the Redskins in their game against the Philadelphia Eagles on November 18, where he had a significant impact early in the game registering one interception and multiple hard hitting tackles, but left in the second half with a right knee injury. It was confirmed the next day that Meriweather suffered a right ACL tear and would miss the remainder of the 2012 season on injured reserve.[20][21]

In his 2013 debut against the Green Bay Packers, Meriweather gave running back Eddie Lacy a concussion after having helmet-to-helmet collision and later gave himself a concussion after another helmet-to-helmet hit with James Starks.[22] After Week 2 game, he was fined $42,000 for the helmet-to-helmet hit on Lacy.[23] In the Week 7 game against the Chicago Bears, Meriweather was penalized for two illegal hits on receivers, Brandon Marshall and Alshon Jeffery.[24] On October 21, 2013, he was suspended for two games because of repeated violations of the league's helmet-to-helmet policy.[25] Two days later, his suspension was reduced to one game.[26] The amended one-game suspension was without pay and cost Meriweather $70,588 of his $1.2 million salary for this season.[27]

During his late October 2013 suspension, Meriweather made comments to the press about how he would need to change his style of play. "I guess I just got to take people's knees out. That's the only way. I would hate to end a guy's career over a rule, but I guess it's better other people than me getting suspended for longer. You just have to go low now, man. You've got to end people's careers. You got to tear people's ACLs and mess up people's knees. You can't hit them high anymore."[28] He also responded to Brandon Marshall's comments towards him getting kicked out the league with "He feel like I need to be kicked out of the league? You know, I feel like people who beat their girlfriends should be kicked out the league, too. So, you tell me who you’d rather have: Somebody who play aggressive on the field, or somebody who beat up their girlfriend? You know, everybody got their opinion, so that’s mine, that’s his."[29][30] The NFL discussed the comments with Meriweather and decided not to take disciplinary action against him.[31]

The Redskins re-signed him to a one-year contract on March 17. 2014.[32] On August 25, 2014, a few days after the Redskins third preseason game, Meriweather was suspended for two games due to an illegal hit on Baltimore Ravens wide receiver Torrey Smith.[33] In a Week 8 win against the Dallas Cowboys, he had a standout performance. In the overtime victory, he recorded two sacks, two forced fumbles, and a fumble recovery after cornerback Bashaud Breeland stripped DeMarco Murray.[34] He was placed on injured reserve on December 19, 2014.[35]

On April 25, 2012, Meriweather was arrested in Arlington County, Virginia, on suspicion of driving while intoxicated, according to a press account. Meriweather was initially stopped for speeding on westbound I-66, according to Arlington County Police spokesman Dustin Sternbeck, who also said that officers detected an odor of alcohol on his breath and performed a field sobriety test, which Meriweather failed. Sternbeck further stated that Meriweather refused a breathalyzer test, was arrested and spent the night in the Arlington County jail. According to the press account, "Police say Meriweather claimed he was driving home from a club in D.C., but couldn’t remember the name of the club."[37]